Spontaneous apoptosis in gallbladder carcinoma: Relationships with clinicopathologic factors, expression of E-cadherin, bcl-2 protooncogene, and p53 oncosuppressor gene

BACKGROUND. Although valuable information regarding spontaneous apoptosis in various human cancers has recently been obtained, spontaneous apoptosis in carcinoma of the gallbladder has not been studied. METHODS. Apoptotic cells were visualized using the nick end labeling method in 49 cases of gallbladder carcinoma. The relationships between frequency of apoptosis, which was expressed as the maximal apoptotic index (MAI), and clinicopathologic factors, immunoreactivity of E-cadherin (E-CD), bcl-2 protooncogene, and p53 oncosuppressor gene were investigated. RESULTS. MAI was significantly correlated with the maximum dimension of the tumor (P = 0.020) and high T category (P = 0.034). A closer correlation between high MAI and high T category was observed in E-CD positive cases (P = 0.0035), whereas no such correlation was evident in E-CD negative cases (P = 0.536). No relationship was observed between MAI and age, sex, histology, grading, stromal volume, venous or lymphatic permeation, and lymph node status. Overexpression of bcl-2 and p53 was observed in 18.4% (9 of 49) and 34.7% (17 of 49) of the cases, respectively, and there was a positive correlation between bcl-2 and p53 (P=0.035). No notable relationship was observed between apoptosis and overexpression of bcl-2 or p53. CONCLUSIONS. These results indicate that the frequency of apoptosis may increase with the progression of gallbladder carcinoma, and in this process, cell-to-cell interaction may affect the cancer's capacity to undergo apoptosis. Oncogenic changes of bcl- 2 and p53 may play a role in tumorigenesis of gallbladder carcinoma, but such changes were not correlated with spontaneous apoptosis.